Imperial College London
Dr Kate C. Tatham

Dr Kate C. Tatham

Faculty of Medicine, Department of Surgery & Cancer

Honorary Clinical Senior Lecturer
 
 
 
//

Contact

 

k.tatham

 
 
//

Location

 

Chelsea and Westminster HospitalChelsea and Westminster Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Ng:2023:10.1038/s41586-023-05771-9,
author = {Ng, K and Boumelha, J and Enfield, KSS and Almagro, JL and Cha, HM and Pich, O and Karasaki, T and Moore, D and Salgado, R and Sivakumar, M and Young, G and Molina-Arcas, ML and de, Carne Trecesson S and Anastasiou, P and Fendler, AC and Au, L and Shepherd, STC and Martinez-Ruiz, C and Puttick, C and Black, JRM and Watkins, TBK and Kim, H and Shim, S and Faulkner, N and Attig, JA and Veeriah, S and Magno, NJ and Ward, ST and Frankell, A and Al, Bakir M and Lim, E and Hill, M and Wilson, G and Cook, D and Birkbak, N and Behrens, A and Yousaf, N and Popat, S and Hackshaw, A and TRACERx, C and CAPTURE, C and Hiley, CT and Litchfield, K and McGranahan, N and Jamal-Hanjani, M and Larkin, J and Lee, S-H and Turajlic, S and Swanton, C and Downward, J and Kassiotis, G},
doi = {10.1038/s41586-023-05771-9},
journal = {Nature},
pages = {563--573},
title = {Antibodies against endogenous retroviruses promote lung cancer immunotherapy},
url = {http://dx.doi.org/10.1038/s41586-023-05771-9},
volume = {616},
year = {2023}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.
AU  - Ng,K
AU  - Boumelha,J
AU  - Enfield,KSS
AU  - Almagro,JL
AU  - Cha,HM
AU  - Pich,O
AU  - Karasaki,T
AU  - Moore,D
AU  - Salgado,R
AU  - Sivakumar,M
AU  - Young,G
AU  - Molina-Arcas,ML
AU  - de,Carne Trecesson S
AU  - Anastasiou,P
AU  - Fendler,AC
AU  - Au,L
AU  - Shepherd,STC
AU  - Martinez-Ruiz,C
AU  - Puttick,C
AU  - Black,JRM
AU  - Watkins,TBK
AU  - Kim,H
AU  - Shim,S
AU  - Faulkner,N
AU  - Attig,JA
AU  - Veeriah,S
AU  - Magno,NJ
AU  - Ward,ST
AU  - Frankell,A
AU  - Al,Bakir M
AU  - Lim,E
AU  - Hill,M
AU  - Wilson,G
AU  - Cook,D
AU  - Birkbak,N
AU  - Behrens,A
AU  - Yousaf,N
AU  - Popat,S
AU  - Hackshaw,A
AU  - TRACERx,C
AU  - CAPTURE,C
AU  - Hiley,CT
AU  - Litchfield,K
AU  - McGranahan,N
AU  - Jamal-Hanjani,M
AU  - Larkin,J
AU  - Lee,S-H
AU  - Turajlic,S
AU  - Swanton,C
AU  - Downward,J
AU  - Kassiotis,G
DO  - 10.1038/s41586-023-05771-9
EP  - 573
PY  - 2023///
SN  - 0028-0836
SP  - 563
TI  - Antibodies against endogenous retroviruses promote lung cancer immunotherapy
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-023-05771-9
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000991048500006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://www.nature.com/articles/s41586-023-05771-9
UR  - http://hdl.handle.net/10044/1/110444
VL  - 616
ER  -
Download